In this request for an ADAMHA Physician Scientist Award an organized program of supervised research, training, and instruction is designed to promote expertise in the application of Positron Emission Tomography (PET) to the study of psychiatric disorders. In the research program, PET will be used to elucidate the neurobiology of panic disorder. In the first phase PET will provide quantitative, regional measurements of cerebral blood flow (CBF), oxygen utilization (CMRO2), and the permeability-surface area product for water (PSw). Under normal conditions, CBF and CMRO2 are coupled to local neuronal activity. In animals, PSw is regulated by the central noradrenergic system and is consistently increased by anti-panic medications. Patients with panic disorder and normal controls will be studied before and during the infusion of sodium (DL) lactate. This technique induces an anxiety attack in the majority of patients, but rarely does so in normal controls. Patients will be studied before and after chronic treatment with antipanic medications. First-degree relatives will be studied as well. In the second phase, PET will also provide measurements of acid-base status in the brain (ABS). ABS is regulated by beta-adrenergic activity and has been implicated in the generation of anxiety attacks. PET measurements will be made before and during additional challenges in order to extend earlier findings and confirm or refute theories which implicate locus coeruleus activation, beta-adrenergic stimulation, and ABS alterations in the generation of panic. These studies will extend our preliminary findings of both an abnormal left-right parahippocampal asymmetry in patients who are vulnerable to lactate-induced panic and a reduction in whole brain PSw during lactate-induced panic. Studies are designed to establish the necessary conditions for the generation of an anxiety attack, to define the physiological actions of anti-panic treatment, and to explore possible genetic markers for panic disorder. This program serves as a paradigm for the application of PET to the study of psychiatric disorders.